The present invention relates to a method for monitoring a condition of a patient under anaesthesia or sedation, the method comprising the steps of: acquiring a signal representing temporally a cardiovascular activity of the patient; detecting periodically repeated waveforms in said signal; calculating at least one parameter selected from: time intervals between, or pressures from, or temporal rates from successive waveforms; and forming respectively at least one of the following: a mathematical time series of said time intervals, or a mathematical pressure series of said pressures, or a mathematical rate series of said temporal rates. The invention also relates to a use of the method, in which a signal representing a cardiovascular activity of a patient is analyzed for detection of periodically repeated waveforms, at least one of the following: time intervals between, or pressures from, or temporal rates from successive waveforms are calculated to provide at least one of the following: a mathematical time series of said time intervals, or a mathematical pressure series of said pressures, or a mathematical rate series of said temporal rates, as well as to an apparatus for monitoring a condition of a patient under anaesthesia or sedation, the apparatus comprising: detection means for receiving a substantially continuous electrical signal representing a cardiovascular activity of the patient; a voltage/current dependent circuit detecting each predetermined waveform in said signal; and first calculation means providing at least one of the following: a series of time intervals between successive waveforms, or a series of pressures, or a series of temporal rates from successive waveforms.
Concept of the depth of anaesthesia has been of interest for recent decades, and several measures have been proposed to assess the depth of anaesthesia. Recently, however, this unitary anaesthesia theory of the existence of one-dimensional concept called xe2x80x9cdepth of anaesthesiaxe2x80x9d has been criticised as oversimplified. Instead it has been suggested that the anaesthesia has not one but three main components: hypnosis, analgesia and muscle relaxation. Different anaesthetic regimens have different effect on these three components. Furthermore, they have effects on both cortical and subcortical levels. An adequate anaesthesia means unresponsiveness to both noxious and non-noxious stimuli. The former may be defined by means of hemodynamic, motor and endocrine stability, while the latter is related to the loss of consciousness and recall and amnesia. In practice the adequate anaesthesia is administered by using a combination of drugs with different effects on brain, spinal cord, autonomic nervous system and neuro-muscular junction. The combination of these effects hence creates the hypnotic, analgesic and muscle relaxing effects.
Heart rate (=HR) is controlled by autonomic nervous system. Especially sympathetic activation to the heart causes heart rate acceleration. Sudden pain causes a stress reaction, which is associated with sympathetic activation leading to sudden increase in HR and blood pressure. Hence, in clinical practise HR and blood pressure responses have been used for decades by experienced anaesthesiologists to heuristically detect inadequacy of anaesthesia. However, not only pain but also various other issues may cause variations in HR and blood pressure, and consequently the HR and blood pressure are continuously varying. Hence, monitoring just the mean level of HR and blood pressure is not sufficient.
Document U.S. Pat. No. 5,372,140 proposes a method and an apparatus for providing a measure of the depth of anaesthesia based on analyzing beat-to-beat heart rate together with respiration. For that purpose a series of so-called R-waves from the cardiac signal is analyzed for determining the position in time of each R-wave relative to the respiratory cycle within which it occurs, and a measurement value representing the degree of clustering is derived. Further a so-called circular statistics is utilized with a test for randomness, and finally the measurement value is compared with a reference value to find the depth of anaesthesia. The proposed measure is related to respiratory sinus arrhythmia, which is primarily controlled by parasympathetic nervous system. The measure is poorly related to the functioning of the sympathetic nervous system, and hence may not measure sympathetic reactions to pain. As a conclusion, the disclosed method and apparatus does not provide results, which could be considered as an objective measure for the level of analgesia of a patient.
Document U.S. Pat. No. 6,120,443 proposes another method and device for determining a depth of anaesthesia by acquiring a plurality of successive signals representing a cardiac activity of the patient, detecting a periodic wave therefrom, calculating time intervals between successive waves, determining a digital series of the time intervals, and calculating a fractal dimension of said series as well as calculating a depth of anaesthesia as a function of the fractal dimension. According to the document the signal is filtered by calculating the maximum correlation between the sampled signal and a theoretical signal, whereupon a signal period between 20 and 80 intervals is suggested, then regrouping the time intervals to form several digital series, and finally the fractal dimension is approximated by determining a dimension of correlation between said digital series, whereupon two to ten series is used. The disclosed method so is mathematically based on computing correlation dimension for beat-to-beat heart rate signal. Theoretically this kind of calculations requires a very long data sequence, leading to large delays in real-time monitoring. Though the inventor proposes to use relatively short data sequences to minimise the acquisition delay this makes the theoretical basis of the method questionable. As above, also this disclosed method and apparatus does not provide results, which could be considered as an objective or reliable measure for the level of analgesia of a patient.
Recently, methods for assessing the hypnotic component especially by monitoring electroencephalographic (EEG) signal have been introduced. The most well-known is the Bispectral Index (BIS), but also fractal spectrum, Lempel-Ziv complexity, Kolgomorov-Sinai entropy and spectral entropy etc. has been studied, e.g. Ira J. Rampil: xe2x80x9cA Primer for EEG Signal Processing in Anesthesiaxe2x80x9dxe2x80x94Anesthesiology, Vol. 87, No. 4, October 1998, and evidently some of them can provide a data describing reliably the level of consciousness independent of the individual. Muscle relaxation may be measured e.g. by monitoring neuro-muscular transmission time and/or excited force, and one method and instrument for this purpose is disclosed in publication EP-0 691 105. Measuring muscle relaxation can be considered to be an established and reliable technology, and it is already a standard practice, because various devices are commercially available, too.
Accordingly the main object of the invention is to achieve a method and an apparatus for monitoring the anaesthesia or sedation of a patient so that a reliable data about level or depth of analgesia would be available to an anaesthetist or to other purposes. The second object of the invention is to achieve a method and an apparatus for monitoring the anaesthesia or sedation capable of using measured signals derived from various sources of the patient, which means that the method should not be dependent on any single type of detector. The third object of the invention is to achieve a method and an apparatus for monitoring the anaesthesia or sedation capable to deliver such results as an output, with the basis of which the adequacy of analgesia could be reliably enough assessed by inexperienced anaesthetists or other operators, too. The fourth object of the invention is to achieve a method and an apparatus for monitoring the anaesthesia or sedation functioning with an acceptable speed so that a change in analgesia to a hazardous direction is detected and reported early enough to allow timely corrective actions.
The above described problems can be solved and the above defined objects can be achieved by the inventive method, which comprises filtering said time series and/or said pressure series and/or said rate series mathematically to provide a plurality of successive average values each over a predetermined first time period, and detecting a substantial decrease, or increase respectively in said plurality of successive average values; and by the inventive use, in which said time series and/or said pressure series and/or said rate series are mathematically filtered to provide a plurality of successive average values each over a predetermined first time period, and a substantial decrease, or increase respectively in said average values is detected and data of said detection is forwarded to an operator for monitoring adequacy of analgesia of a patient under anaesthesia or sedation; as well as by the inventive apparatus, which comprises second calculation means providing successive average values of the series of said time intervals and/or said pressure series and/or said temporal rates over a predetermined first time period, third calculation means providing data about an decrease, or increase respectively in said successive average values, and a display and/or connections into other devices.
The present innovation proposes a method, which enables monitoring a condition of a patient under anaesthesia or sedation, and specifically enables to assess the adequacy of analgesia in anaesthetized or sedated subjects in real time, based on the measurement of sympathetic reactions in beat-to-beat cardiovascular time series or pressure series or heart rate series. In anaesthesia there is a need to assess level of analgesia, i.e. adequacy of pain medication, in order to avoid the subject to feel pain during the operation. This is a complicated task in presence of other medication, such as hypnotic agents and especially muscle relaxants. The invention functions successfully in solving this task and so fills the missing link in the complete anaesthesia monitoring. Especially for analgesia and hypnosis, the adequacy of another is dependent on the level of the other one as schematically shown in FIG. 1. In area D the degree or level of analgesia is acceptable as such, but the degree or level of hypnosis is quite too low, which case corresponds a local analgesia or anaesthesia and is not practical in many cases. In area E the degree of hypnosis is acceptable as such, but the degree of analgesia is quite too low, whereupon the patient does not have consciousness during operation and does not remember anything about the operation afterwards, but the pain of the operation cause traumatic symptoms anyway. In area B the degree of analgesia is high enough so that a lower degree of hypnosis can be utilized, and in area C the degree of hypnosis is high enough so that a lower degree of analgesia can be utilized. In area A both the analgesia and the hypnosis has optimal levels, but generally points on the right hand side of the curve in FIG. 1 are useful and points on the left hand side of the curve shall be avoided during total anaesthesia. For optimal total anaesthesia all the three components, that are analgesia, hypnosis and muscle relaxation should be controlled. This requires methods to independently assess all the components. This innovation is based on the facts that pain causes a sympathetic activation. Sympathetic activation propagates via sympathetic nervous branches to different sites of the body, including heart and blood vessels. In blood vessels the activation causes vasoconstriction and increases hence blood pressure. In the heart sympathetic activation causes heart rate acceleration.
Actual heart rate is defined by the net effect of sympathetic and parasympathetic activity to the heart. An acceleration of heart rate may be caused either by sympathetic activation or withdrawal of parasympathetic activity, or both. A deceleration is caused if opposite changes in activity occurs. The amplitude or levels of the systemic arterial blood pressure behave in an analogous way. A sudden increase of blood pressure is caused by the sympathetic activation, while a decrease is primarily caused by the decrease in the sympathetic activationxe2x80x94in case sudden changes in fluid balance can be excluded. Due to continuous modulation in both sympathetic and parasympathetic activity the beat-to-beat heart rate is continuously varied, which is called heart rate variability (HRV). The presence of HRV complicates the identification of e.g. heart rate accelerations due to sympathetic activation. However, the time constants of the parasympathetic and sympathetic responses are different. For the former the response time is a few hundreds of milliseconds while for the latter the response starts only after a couple of seconds. Hence, it is possible to filter out short-term HRV primarily caused by parasympathetic activity, and hence emphasise the sympathetic activity in the signal. Furthermore, by picking up heart rate accelerations it is further possible to emphasise features, which are most potentially related to sympathetic activation. It should be noted that sympathetic reactions might be caused by other reasons than pain, such as physical exercise, mental stress, drugs, etc., too However, in anaesthetized or sedated subjects these other or external stimuli and factors, in addition to potential pain caused by surgery or care actions, are few and may be largely controlled by the care team. Though the reaction itself is not specific for pain and analgesia, it is possible to discriminate whether the identified reaction was due to pain or not by using this other information available for the care team. Hence, excluding the short-term effects of various drugs, the sympathetic reactions are potential markers for pain, and so concerning anaesthetized and sedated subjects, heart rate accelerations are potential markers for inadequate analgesia. The present innovation proposes a method to quantify the inadequate analgesia through one of the heart rate acceleration indexes and/or a blood pressure index, with the respective intermediates, too.
The present innovation comprises a step of acquiring at least one signal representing the subject""s cardiac activity, a step of detecting the position of a waveform representing each single heart beat in the signal, a step of constructing a beat-to-beat signal by calculating the time difference or temporal rates like frequency of these waveforms, or alternatively a step of calculating the blood pressures of these waveforms, a step for filtering this signal to suppress non-sympathetic variations, a step for detecting potentially sympathetic reactions in the filtered signal, and a step for calculating a statistic related to the said potentially sympathetic reactions.
The signal S can be derived preferably from ECG but also from blood pressure, from blood flow velocity, from a light or other electromagnetic radiation absorption factor of blood, from oxygen content of the blood, from acoustic signal emitted by heart or from any other known or new signal or from any combination of the these signals or other known or new signals, which is dependent on cardiovascular activity of the patient and allows to determine a beat-to-beat property of the heart. As examples FIG. 2A shows a signal S received from ECG generally, and FIGS. 2B and 2C show signals S received from blood pressure generally, and the other signals received from other kind of detections typically resemble these shown signals. In general, any signal, which would allow measuring sympathetic reactions, would do. Because the methods and apparatuses to acquire this kind of signals are generally known this step is not described more in detail.
Detecting the waveform P means finding a specific repeating point in the continuously variable signal acquired corresponding reliably and precisely enough to the beat-to-beat phenomenon or the pressure phenomenon of the heart so that the variable time between successive and similar or respective points of the signal, or the pressure difference between or the level in successive points of the signal can be established. A periodically repeated waveform P in the signal is so to be detected. There exist multitude of known and published methods to do this, and accordingly these methods are not described in detail. These methods include e.g. detection of a specific waveform present in the measured signal and representing a single heartbeat, such as R-wave in ECG, systolic pressure in blood pressure curve, maximum derivative in blood flow or blood pressure signal, etc. Furthermore, the methods include computing cross-correlation function of the signal and defining the inter-beat interval from the successive local maximums of the cross-correlation signal, and using a matched filter for the same purpose, etc. Preferably R-to-R interval (RRI) signal, generally the time interval Ti, which is calculated as a time difference between the successive R-waves, or a heart rate (HR), generally the temporal rate Ri, which is calculated as a frequency between the successive R-waves, is used, as shown in FIG. 2A. Respective time intervals Ti or temporal rates Ri can be determined on the basis of inter-beat-interval (IBI) defined from systolic pressure time instants in blood pressure signal, as shown in FIG. 2B, or the pressures Bi of the pulses on the basis of systolic blood pressure (BP) values in blood pressure signal, as shown in FIG. 2C, or any other known or new waveform. These calculated successive time intervals Ti form a mathematical time series T1, T2 . . . Tnxe2x88x921, Tn, Tn+1 . . . , and respectively these calculated successive temporal rates Ri form a mathematical rate series R1, R2 . . . Rnxe2x88x921, Rn, Rn+1 . . . , or these calculated successive pressures form a mathematical pressure series B1, B2 . . . Bnxe2x88x921, Bn, Bn+1. . . .
The time series and rate series respectively is then mathematically filtered to suppress signal components in the series caused by non-sympathetic activity, and hence to emphasize data corresponding sympathetic activity. In this step e.g. a plurality of successive average values {overscore (T)}i, {overscore (B)}i, {overscore (R)}i are formed from said time series or said rate series. Potentially sympathetic reactions in the filtered data signal can be detected as the shortening of e.g. the R-to-R-interval, or alternatively as the rise or increase of the HR-number, or as the increase of the blood pressure, i.e. the systolic pulses BP or any other levels or amplitudes, which processed data signal can be called a trend signal, which means signal components having a predetermined trend caused by sympathetic activity and so not suppressed. Preferably, only those parts related to potentially sympathetic reactions are restored, the other parts of the samples or time/rate series are suppressed e.g. by assigning them to zero. It shall be understood that there are several mathematical methods to suppress those samples not related to potentially sympathetic reactions and so to produce a trend signal describing sympathetic activity.
The statistic emphasising the potentially sympathetic reactions is calculated after above mentioned detection step. Preferably this is achieved by e.g. calculating a windowed sliding sum of the trend signal, which was formed in the previous step. Alternatively or in addition, a threshold may be used and only trend signals greater than the predetermined threshold are included. The statistic may also be normalised for example by setting the reference value to some well-defined period during the monitoring, or to some reference value obtained from larger studies.
The data concerning the detected decrease, or increase respectively of said average values, that is the emphasized data, is finally forwarded to an anaesthetist or other operator for monitoring adequacy of analgesia of a patient under anaesthesia or sedation. Further and according to requirements of operation also data describing muscle relaxation of said patient and/or data describing the loss of consciousness, together with the above described data of detection concerning analgesia, are forwarded to the operator. It is also possible to measure and receive signals S to provide two or all three of the variables discussed, that is time intervals and/or heart rates and/or pressures of cardiovascular activity and perform the respective calculations, and finally report the results or some of the intermediate results with or without their comparison to the anaesthetist/operator or to some other use. Most probable, if necessary, is the measuring of pressures Bi and in addition either time intervals Ti or temporal rates Ri with respective further calculations, because the meanings of two latter time variables are in fact identical, while the meaning of pressure variables may be deviating. In any case at least one of these three signals is acquired and the respective variables Ti, or Bi, or Ri is calculated with further calculations and analysis.
The apparatus according to the invention is provided with proper detector(s) for receiving a substantially continuous electrical signal S representing a cardiovascular activity of the patient, electrical circuits capable of detecting the predetermined points P in the signal, and proper calculation means, e.g. micro-processors, capable of performing the necessary calculations, as well as a display and/or connections for reporting those results and/or intermediate results of calculations needed. Useful components for the apparatus are commercially available, and so they are not described in detail.